In the fields of medical diagnosis or drug-based therapy, the concentration measurement of analytes of anesthetics or harmful chemicals has recently been useful in medical or environmental fields. Above all, the concentration measurement of biological samples used in the fields of medical diagnosis and therapy is drawing increasing interest along with an increase in human desire to be free from various diseases. Particularly, with regard to diabetes, a glycated hemoglobin test capable of measuring blood sugar allows a relatively long-term average value of the blood sugar to be obtained by one measurement, and thus is drawing increasing interest.
It has been known that diabetes, which is one cause of adult kidney disease, can reduce the expected value of a mean life span by 15 years. The control of blood sugar to a lower value has been known to be able to prevent chronic complications caused by diabetes.
Hemoglobin A1c (Hb A1c) is called glycated hemoglobin, and is present in red blood cells as a part of hemoglobin. When a concentration of blood sugar (glucose) in blood is raised, a glucose moiety is conjugated to hemoglobin. This hemoglobin conjugated with the glucose is referred to as glycated hemoglobin or Hb A1c. A value of the glycated hemoglobin is in equilibrium with a value of blood sugar over the last two to three months, and thus the glycated hemoglobin value may be recognized as the blood sugar value for the last two to three months. The glycated hemoglobin value is checked and used as an index for glycosuria management and future drug control. As such, it is important to measure the glycated hemoglobin.
The glycated hemoglobin has a structure in which the glucose is conjugated to the N-terminal valine in the β-chain hemoglobin in the blood, and only a glucose moiety must be specifically detected and measured to distinguish it from the hemoglobin. This moiety is measured in a variety of methods, of which a method using an antibody and borate affinity chromatography are widely used.
To quantitatively measure the glycated hemoglobin value, a fraction of an amount of glycated hemoglobin on the basis of an amount of total hemoglobin is given because the amount of total hemoglobin is different for everyone. Here, the amount of total hemoglobin is measured together. The amount of total hemoglobin generally has a range of 13.0 to 17.0 g/dl for adult men, a range of 12.0 to 15.0 g/dl for adult women, and a range of 11.0 to 14.0 g/dl for infants. When the glycated hemoglobin value is 6.0%, it may be expressed that three-month blood sugar is maintained to 120 g/dl on average. The American Diabetes Association (ADA) recommends that the glycated hemoglobin value be maintained to 7.0% or less, and a normal range thereof is 4.0 to 6.5%.
Meanwhile, in U.S. Pat. Nos. 5,242,842, 6,339,293, and 6,300,142, a signal generation material such as a dye is additionally required, and thus a measuring step is troublesome. In JP3340129, a diluting step is additionally required. Thus, additional steps must be performed as well. That is, this work requires a measurer to directly intervene in several steps, which may be troublesome to the measurer. Further, the intervention of the measurer may complicate a measuring process, and thus a measuring time is delayed.
Accordingly, there is a need for a method for easily measuring a concentration of the glycated hemoglobin in the whole blood sample by performing a further simplified procedure.